Vaccines have led to many of the world's greatest public health triumphs, but many deadly viruses, such as HIV, elude the best efforts to develop effective vaccines. An improved understanding of how the immune system operates during a viral infection is critical to designing successful anti-virus vaccines, particularly those designed to elicit T cells, which have the ability to kill virus infected cells before progeny viruses are produced. Many vaccines are delivered in the skin or muscle, where they initiate immune responses in draining lymph nodes. To better understand how live virus vaccines activate T cells, we are using a multiphoton microscope to visualize the interaction of T cells with viruses in living mice. In 2015 our studies have demonstrated a function for CXCR3 in enhancing the ability of tissue-localized CD8(+) T cells to locate virus-infected cells and exert anti-viral effector functions.